A sensitive histochemical method for the visualization of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity was used to determine the laminar distribution of cholinesterase-positive cortical tangles in Alzheimer's disease (AD). In many cortical areas AChE- and BChE-positive tangles displayed a completely overlapping distribution. In other areas the most superficial layers contained only AChE-positive tangles whereas the deepest layers contained only BChE-positive tangles. These observations suggest that some cholinesterase-positive tangles have a predominantly (if not exclusively) AChE-like reactivity whereas others have a reactivity that is predominantly BChE-like. The intermingling of AChE- and BChE-positive tangles in most cortical areas and layers suggests that there may also be a third population in which the two enzymes are equally prominent in the same tangle.